It has been recognized for some time that early onset periodontal diseases (EOP) aggregate in families. Recent genetic epidemiological studies indicate that this aggregation may be due to at least in part to the action of a gene or genes that have a major influence on individuals' susceptibility to developing EOP. For several years our group has been conducting family studies of EOP. Our studies and those of our collaborators have identified a large number of individuals affected by this disorder and we have recruited many of these individuals and both EOP affected and unaffected members of their extended families into participation in our study. These investigations have led to our establishment of a large collection of immortalized cell lines and DNA samples from EOP affected individuals and their families. This proposal is designed to capitalize on this valuable resource by conducting molecular genetic studies with the goal of identifying some of the specific genes and the biochemical and physiological processes that underlie risk of EOP. Our specific aims are: i.) to apply linkage analysis techniques to EOP affected families using highly informative microsatellite repeat polymorphisms, in order to map the location of susceptibility genes of major effect, and ii.) to conduct linkage and association studies using DNA polymorphisms genotyped by RFLP and PCR methods for loci in the vicinity of selected candidate genes of the immune system e.g., HLA, TCR, IG, cytokines, etc.) and chemotactic receptors.